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Reviews and Overviews

Remission in Schizophrenia:
Proposed Criteria and Rationale for Consensus

Nancy C. Andreasen, M.D., Ph.D. New advances in the understanding of group reviewed available definitions and
schizophrenia etiology, course, and treat- assessment instruments to provide a con-
ment have increased interest on the part ceptual framework for symptomatic, func-
William T. Carpenter, Jr., M.D.
of patients, families, advocates, and pro- tional, and cognitive domains in schizo-
fessionals in the development of consen- phrenia as they relate to remission of
John M. Kane, M.D. sus-defined standards for clinical status illness. The first consensus-based opera-
and improvement, including illness remis- tional criteria for symptomatic remission
Robert A. Lasser, M.D. sion and recovery. As demonstrated in the in schizophrenia are based on distinct
area of mood disorders, such standards thresholds for reaching and maintaining
Stephen R. Marder, M.D. provide greater clarity around treatment improvement, as opposed to change crite-
goals, as well as an improved framework ria, allowing for alignment with traditional
Daniel R. Weinberger, M.D. for the design and comparison of investi- concepts of remission in both psychiatric
gational trials and the subsequent evalua- and nonpsychiatric illness. This innovative
tion of the effectiveness of interventions. approach for standardizing the definition
Unlike the approach to mood disorders, for outcome in schizophrenia will require
however, the novel application of the further examination of its validity and util-
concept of standard outcome criteria to ity, as well as future refinement, particu-
schizophrenia must reflect the wide heter- larly in relation to psychosocial and cog-
ogeneity of its long-term course and out- nitive function and dysfunction. These
come, as well as the variable effects of criteria should facilitate research and sup-
different treatments on schizophrenia port a positive, longer-term approach to
symptoms. As an initial step in developing studying outcome in patients with schizo-
operational criteria, an expert working phrenia.

(Am J Psychiatry 2005; 162:441449)

T he Remission in Schizophrenia Working Group was


convened in April 2003 to develop a consensus definition
come measure is limited because of the variability of base-
line symptom intensity across interventional trials. Specif-
of remission as applied to schizophrenia. The need for ically, the proposed remission criteria define remission as
such a definition is timely because of recent insights into a low-mild symptom intensity level, where such absent,
and expectations around the long-term course of schizo- borderline, or mild symptoms do not influence an individ-
phrenia, including the evolution of psychosocial and uals behavior. Such symptom thresholds have sometimes
pharmacological therapies for psychotic disorders, vari- also been augmented by functional improvement criteria
able definitions of treatment outcome in schizophrenia, in a variety of previous definitions of remission or recovery
and evidence that traditional predictions of generally poor in schizophrenia (47), but this working group chose to fo-
outcome may have been overstated. In addition, the po- cus solely on symptomatic remission for reasons de-
tential utility of a consensus definition of remission in scribed subsequently.
schizophrenia has been reinforced by the successful appli- Precedents for remission criteria exist for both psychiat-
cation of remission and recovery concepts to the treat- ric and nonpsychiatric illnesses. Traditionally, remission
ment of patients with mood and anxiety disorders. criteria in nonpsychiatric illnesses have been character-
The working group sought to develop operational crite- ized by the abatement of disease symptoms. For example,
ria for remission, using as a model consensus work in complete remission in non-Hodgkins lymphoma requires
mood and anxiety disorders conducted over the past de- the patient to be in normal health without evidence of
cade (13). In this consensus, remission was defined by lymphoma, with no lymph nodes larger than 1.5 cm in the
using an absolute threshold of severity of the diagnostic long axis on computerized tomography scans, although
symptoms of schizophrenia, rather than percentage im- this node size is larger than normal in a person without
provements from a particular baseline. This shift in char- lymphoma (8). Similarly, remission in rheumatoid arthri-
acterizing improvement through means of threshold cri- tis is defined as the absence of fatigue, as well as negligible
teria will permit direct cross-trial comparisons. The real- morning stiffness, and a lack of joint pain, tenderness, and
world interpretability of change scores as a primary out- soft tissue swelling, accompanied by a normal erythrocyte

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REMISSION IN SCHIZOPHRENIA

sedimentation rate (9). Comparatively, remission may be (7), as well as an evolving appreciation for the relationship
characterized by the complete absence of symptoms in ill- between improvements in symptoms, cognition, and
nesses for which treatment is clinically oriented toward functionality. Because cognitive impairments in schizo-
cure, versus illnesses for which treatment is oriented to- phrenia are of a continuous nature (in contrast to the epi-
ward remission-recovery as the clinical goal. sodic intensity of psychotic symptoms) and because the
In the case of noncurable, progressive illnesses with association of specific symptoms with specific cognitive
psychiatric and nonpsychiatric components, such as mul- deficits remains under active investigation, it is not yet
tiple sclerosis, consensus on remission as an absence of possible to incorporate an extensive knowledge base re-
symptoms has not been achieved. Here, the majority garding psychosocial or cognitive dysfunction into defini-
(85%) of relapsing-remitting multiple sclerosis is termed tions of remission or recovery in schizophrenia.
secondary-progressive multiple sclerosis, where remis-
sions are often associated with some symptomatic resid- Remission Criteria
ual dysfunction (10). To date, remission in psychiatric ill- in Mood and Anxiety Disorders
nesses, such as anxiety disorders, has been objectively
defined not by the complete absence of anxious or depres- In developing criteria for remission in schizophrenia,
sive symptoms but rather by minimal symptoms with mild the working group used as a model the development of
disability (11). One consensus challenge regarding remis- criteria for disease state and change criteria in mood and
sion in schizophrenia surrounds the recognition that al- anxiety disorders, particularly major depressive disorder.
though the symptoms of many anxiety and depressive dis- Early clinical trials of antidepressant therapies were char-
orders coexist with normal life experience, the commonly acterized by inconsistent definitions of change criteria,
recognized symptoms of schizophrenia lie outside this ex- leading in turn to inconsistent evaluations of therapeutic
perience. However, there is some evidence for the conti- approaches (1). The development of the Hamilton De-
nuity of psychotic symptoms (e.g., delusions and halluci- pression Rating Scale in 1960, its refinement over succeed-
nations) with normal experience (12, 13), and negative ing years, and its gradual incorporation as a standard
symptoms (e.g., avolition, alogia) clearly are on a contin- measure in clinical trials provided clinical researchers
uum with normality. with a consistent tool to assess change in symptoms over
In recent years there has been an appropriate increase time (14). However, despite the use of standardized, vali-
in emphasis on clinical outcomes that are meaningful to dated rating scales for symptom and disease severity,
patients, families, and clinicians, as well as a greater focus inconsistent use and application of terms such as re-
on functional recovery. For a disorder such as schizophre- currence, relapse, response, remission, and recovery re-
nia, complete recovery implies the ability to function in mained widespread. Response, in particular, was used as
the community, socially and vocationally, as well as being the defining measure of treatment efficacy in clinical trials
relatively free of disease-related psychopathology. Recov- of most new pharmacological agents, resulting in a thera-
ery is conceptualized, therefore, as a more demanding and peutic focus on short-term improvements and providing
longer-term phenomenon than remission, consistent with little guidance to clinicians regarding long-term disease
the work of various research groups (7, 14). Remission is a management.
necessary but not sufficient step toward recovery. The Recognizing the clinical need for consistency in defin-
working group chose to define remission as a state in ing outcomes, particularly for chronic mental illness, a
which patients have experienced an improvement in core task force on the psychobiology of depression was con-
signs and symptoms to the extent that any remaining vened by the MacArthur Foundation in 1988 to evaluate
symptoms are of such low intensity that they no longer in- historical descriptions of change criteria and to develop
terfere significantly with behavior and are below the internally consistent, empirical definitions, as well as op-
threshold typically utilized in justifying an initial diagnosis erational criteria, for response, remission, and recurrence
of schizophrenia. The working group struggled with the in major depressive disorder (1). This effort was based on
decision of whether the complete absence of any core a conceptualization approach that moved from the rec-
signs and symptoms should be required, but on balance ognition of change criteria as a valid construct, through
the group felt that the proposed threshold described definitions of these change criteria, to operational criteria
herein was the most appropriate, on both clinical and for their assessment (1). In addition to developing defini-
heuristic grounds. tions for these clinical concepts, this task force suggested
Consensus regarding operational criteria for recovery, methods through which their utility could be assessed, in-
which might include improvements in cognition or psy- cluding reanalysis of existing data and prospective studies
chosocial functioning, was considered outside the scope using outcomes guided by the new criteria (1).
of the working group, because more research is needed on The task force examining major depressive disorder in-
this topic. As mentioned earlier, such criteria are the focus corporated criteria for both disease severity and duration
of ongoing multidisciplinary efforts seeking to incorpo- of improvement and suggested that the instruments used
rate the viewpoints of patients, caregivers, and clinicians for symptom severity assessments be test-retest reliable,

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ANDREASEN, CARPENTER, KANE, ET AL.

easily completed in a clinical setting, and able to provide considering possible definitions of remission in schizo-
value in establishing a prognosis for future disease course phrenia, important features include applicability to clini-
(1). The task force proposed a definition for remission, cal practice across a wide range of treatment settings,
based on the 17-item Hamilton depression scale total utility in research settings, and incorporation of both
score, as maintenance of an endpoint score of 7 for at symptom severity and time components.
least 2 but less than 6 months. To facilitate broader accep-
tance of the remission concept, criteria based on the Application of the Conceptualization
Schedule for Affective Disorders and Schizophrenia and
Approach to Schizophrenia
the Beck Depression Inventory were also proposed.
During the past decade, the definition of symptomatic Schizophrenia and other psychotic disorders differ sub-
remission in major depression has been incorporated into stantially from mood disorders in both disease character
clinical studies of treatment efficacy, confirming that re- and disease course, and any definition of remission in
mission is a more stringent standard than response and schizophrenia should reflect these characteristic differ-
suggesting that remission can be used in conjunction ences. For many years, schizophrenia was regarded as a life-
with, or even to replace, other outcomes in efficacy evalu- time chronic illness with little or no hope of recovery. In
ations (15). In addition, the remission concept has facili- fact, dramatic improvement in a patient with a diagnosis of
tated comparisons of therapeutic success not only be- schizophrenia was regarded by many clinicians as evidence
tween pharmacological agents but also across a wide of original misdiagnosis (4). The refinement of knowledge
spectrum of treatment modalities, encompassing psy- regarding the clinical course of schizophrenia, improve-
chosocial and biological approaches, alone and in com- ments in psychotherapeutic techniques, and the introduc-
bination (16, 17). Recent updates by the Depression and tion of antipsychotic medications began to alter this view,
Anxiety Working Group have resulted in expansion of the with consideration of possible parameters to define recov-
remission concept to encompass sustained symptom re- ery appearing in the literature as early as 1983 (22).
mission during the maintenance phase, in order to sup- Psychosocial and vocational therapies have also played
port clinical emphasis on extending and maintaining clin- a critical role in improving long-term outcome. The effec-
ical improvement. To this end, specific time frames have tiveness of family treatment, cognitive behavior therapy,
been applied to the remission definition during these and rehabilitation models has been demonstrated in a
phases (18). range of settings and clinical trial models (2325). In addi-
The successful implementation of the conceptualization tion, assertive case management has received increased
approach to defining change criteria in major depression attention as a mechanism to prevent and resolve major so-
has led to similar efforts in panic disorder (18), treatment- cial needs and crises (26). In the United States, however,
resistant depression (19), generalized anxiety disorder (20), the availability of such key supports varies substantially
and eating disorders (21). In general, these efforts initially between localities, and social and vocational interven-
emphasized symptomatic improvements, rather than func- tions are seldom applied in a manner consistent with op-
tional improvement, as the primary criteria for defining re- timal clinical outcome (23, 25, 27).
mission; the evaluation of functional improvement has There also now exists a range of pharmacological and
generally been incorporated into definitions of recovery nonpharmacological interventions with proven effective-
and wellness. In generalized anxiety disorder, for exam- ness, but with variable effect on specific disease features;
ple, response and remission are defined, respectively, as a pharmacological treatments are also characterized by
reduction in and sustained control of symptoms rated with substantial differences in the nature and severity of ad-
the Hamilton Anxiety Rating Scale. In contrast, the defini- verse effects (2830). This variability highlights the need
tion of recovery requires sustained symptom remission for and importance of establishing criteria for clinical im-
along with return of function to near-normal levels (with provement that can be applied across multiple treatment
some disease vulnerability); wellness is further defined as modalities and specific therapies.
functional normality in the absence of disease (20). In addition to the development of improved therapeutic
In summary, the development and use of remission cri- options, the disease course of schizophrenia has been
teria in mood disorders is instructive for the development more fully characterized in recent years. Although schizo-
of similar criteria as applied to schizophrenia. The appli- phrenia exhibits substantial heterogeneity with respect to
cability to schizophrenia is based on the proven utility of severity and course over time, typical features of disease
operationalized remission criteria in redefining treatment course have been summarized, with support from models
expectations to raise the bar for existing and novel ther- presenting schizophrenia as a neurodevelopmental disor-
apies, in enhancing study design and facilitating cross- der with a substantial hereditary component (31). From a
study comparisons, in providing a single benchmark for premorbid stage characterized by nonspecific cognitive,
longitudinal assessments of disease course, and in re- motor, and social impairments, patients move into an ex-
casting concepts of long-term care of patients with mood tended prodromal stage during which mood, cognitive,
disorders in terms of a positive, attainable outcome. In psychosocial, and even mild psychotic symptoms of vary-

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REMISSION IN SCHIZOPHRENIA

ing severity and duration may appear. The targeting of the emergence of nuanced insights into the etiology,
these early stages for therapeutic intervention, however, pathophysiology, and disease course in schizophrenia,
has been frustrated by the nonspecificity of the symptoms based on extensive longitudinal research and recent
and their lack of predictive value (31). Attempts at early genetic findings;
treatment have highlighted the substantial duration of the availability of increasingly effective psychothera-
time commonly elapsing between symptom onset and di- peutic and pharmacological options for treating
agnosis in first-episode schizophrenia. Although most pa- schizophrenia, including oral and long-acting atypical
tients improve significantly after their first episode is antipsychotic medications;
treated, the majority experience subsequent episodes, the need to facilitate standardized comparisons across
with only a small fraction being able to regain premorbid treatments and therapeutic modalities, especially
levels of functionality (32). given the ongoing lack of clinically relevant clarity in
The cycle of relapse, often accompanied by noncompli- comparing different treatments on the basis of clinical
ance with treatment or suboptimal treatment, produces trials that use percent improvement from baseline as
incomplete or unsustained symptom remission in many an efficacy measure; and
patients. This condition may subsequently lead to chronic the opportunity that such a definition provides to ele-
illness characterized by substantial morbidity and persis- vate and more clearly articulate expectations on the
tent deficits in cognition and psychosocial function. Al- part of patients, caregivers, and mental health provid-
though this progressive downward spiral is characteris- ers for positive long-term outcome in schizophrenia.
tic for some patients, others may experience a relatively
Additional impetus for working toward a consensus def-
circumscribed deterioration early in the illness, with
inition of remission is provided by prospective and retro-
symptomatic and functional status stabilizing thereafter
spective studies (7, 3439), many of which are recent, that
(31). Practice guidelines developed by the American
define remission and recovery using a range of criteria (Ta-
Psychiatric Association codified a three-phase model of
ble 1). Although the symptom-based criteria used in these
schizophrenia disease course, with the recognition that
studies are a marked improvement over the generalized
these phases merge into one another without absolute,
descriptions (such as mild illness or no active psycho-
clear boundaries between them (33). In this model, the
sis) that predominated in earlier literature, the lack of
acute phase, characterized by florid psychosis and se-
consistent definitions prevents cross-study comparison
vere positive and/or negative symptoms, is followed by a
and limits the generalizability of results.
stabilization phase, during which symptoms recede and
decrease in severity, and a subsequent stable phase with
reduced symptom severity and relative symptom stability. Current Research in Remission
According to these guidelines, the majority of patients al- and Recovery in Schizophrenia
ternate between acute psychotic episodes and stable
Recent efforts to describe remission in schizophrenia
phases with full or partial remission (33), although the
have been based on longitudinal symptom evaluation
operational criteria for remission remain undefined. Also combined with a defined time threshold in early-episode
unclear is the extent to which symptomatic remission or acutely ill populations. However, most of these studies
must occur in order to achieve improved functioning and were designed with the goal of identifying prognostic fac-
ultimately recovery and autonomy. Regardless of clinical tors for the likelihood of remission, rather than establish-
course, it can be argued that current treatment perspec- ment of operational remission criteria (3437). Studies of
tives are constrained by a view of schizophrenia focused individuals with chronic schizophrenia have used more
on preventing relapse, in contrast to therapy goals for variable criteria for remission, including time without
which long-term symptom remission serves as a founda- hospitalization, decreased delusional thought, and im-
tion for building functional gains. proved insight into illness, with these definitions less often
In light of substantial improvements in understanding including a time threshold (7, 38, 39) (Table 1). However,
schizophrenia and its treatment options, the working the widespread use of continuous symptom-based assess-
group posited that symptomatic remission is a definable ment instruments to characterize degree of improvement
concept and an increasingly achievable stage in the treat- in patients with schizophrenia suggests that it is an appro-
ment of schizophrenia, serving to expand the current ceil- priate time to define categories of achieved clinical status
ing of patient progress beyond stability. Further, the im- based on those instruments.
portance of defining a remitted state is highlighted by the The working group concluded that any definition of re-
observation that psychosocial therapies and rehabilitation mission in schizophrenia should include a significant time
are most effective when positive and negative symptoms component and be applicable to patients across stages of
are adequately controlled. The working group concluded disease course. This approach suggests that assessment
that progress toward an operational definition of remission instrument(s) used in the definition of remission should
in schizophrenia is warranted at this time because of be objective and consistent with regard to test-retest re-

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ANDREASEN, CARPENTER, KANE, ET AL.

TABLE 1. Studies Defining Criteria for Remission in Schizophrenia


Study Year Criteria for Remission
Studies defining remission in populations
with chronic schizophrenia
Curtis et al. (38) 2001 In a single time point evaluation, Brief Psychiatric Rating Scale (BPRS) total score of <30;
scores of <3 (moderate) on the affective flattening item and <2 (mild) on the alogia,
anhedonia, avolition, and attention items of the Scale for the Assessment of Negative
Symptoms (SANS); Global Assessment of Functioning scale score of >60; no psychotic
symptoms for more than 1 month; no hospitalization for 3 months; no more than one
residual symptom; presence of employment; and association with friends.
Liberman et al. (7) 2002 BPRS positive and negative symptom item scores of 4 (moderate) over 24 months
duration.
Yen et al. (39) 2002 Any one of three Positive and Negative Syndrome Scale subscales (positive, negative,
general psychopathology) with a mean score of 2 (minimal) at a single time point
evaluation.
Studies defining remission in populations
with early-episode or acute schizophrenia
Lieberman et al. (34) 1993 Schedule for Affective Disorders and Schizophrenia, Change Version, psychotic and
disorganization items, positive symptom item score of 3 (suspiciousness, delusions,
hallucinations, impaired understandability, bizarre behavior); Clinical Global
Impression (CGI) severity scale score of 3; CGI global impression of change score
of 1 or 2 for 8 consecutive weeks; full remission when no residual positive symptoms
and scores of 2 (mild) on all SANS negative symptom global items.
Amminger et al. (35) 1997 Absence of hallucinations, delusions, thought disorder, and catatonic behavior
for 8 consecutive weeks.
Eaton et al. (36) 1998 Absence of Interim Follow-Up Schedule-defined criteria (hallucinations, delusions,
thought disorder, extreme psychomotor disorder) for at least 3 months.
Ho et al. (37) 2002 Scale for the Assessment of Positive Symptoms positive symptom global items score
of 2 (mild) on psychotic and disorganized dimensions for 8 consecutive weeks.

producibility. A symptom-based, validated assessment in- group therefore concluded that a consensus definition of
strument provides the necessary objectivity, consistency, symptomatic remission, followed by broad dissemination
and independence to enable clinicians and researchers to and use in both research and clinical settings, would in
define remission after a first episode and subsequent psy- turn facilitate the subsequent development of a consensus
chotic episodes and throughout periods of chronic, non- definition of remission or recovery that includes cognitive
acute illness. In addition, such instruments can be used to and functional outcomes.
evaluate longitudinal status and to support a shifting fo-
cus from acute treatment to the continuation and mainte- Development of Criteria for Remission
nance phases in long-term care.
in Schizophrenia
The working group explicitly considered the incorpora-
tion of symptomatic, functional (activities of daily living, As a starting point, the working group reviewed the his-
social relationships, employment, quality of life), and cog- torical constructs for schizophrenia, as well as subsequent
nitive outcomes into the definition of remission. The paral- studies that used factor analysis to examine the illness
lel work conducted in mood and anxiety disorders, and the construct (4051). For many years categorical approaches
observation that longer-term symptomatic quiescence is a were used to identify and classify disease types and sub-
common, but not absolute, prerequisite for functional im- types. The traditional categorical Kraepelinian subtypes
provement, suggest that a two-phase model for patient have formed the basis for the DSM approach to classifying
outcomes (remission followed by recovery) may character- schizophrenia in all its recent editions. Although these
ize these illnesses well and may potentially be applicable to classifications were retained in DSM-IV, an alternative di-
schizophrenia as well at some time in the future. However, mensional approach was also carefully considered and in-
as described earlier, an adequate knowledge base is not yet cluded in the appendix for future consideration.
available concerning the long-term course of cognitive and Categorical and dimensional approaches have impor-
psychosocial outcomes in schizophrenia and their rela- tant conceptual differences. Although categories divide
tionship to changes in symptom patterns and severity. Fur- patients into groups, dimensions divide symptoms into
ther, working group consensus recognized that the course groups. Categorical approaches tend to have the problem
of schizophrenia may often be quite complex and present that patients disorders often do not present in classic
significant challenges to creating a criterion-based defini- pure forms. Dimensional approaches recognize the fact
tion incorporating function and cognitive components. that symptom groups overlap in individual patients (40).
That is, functional improvement can occur in some pa- The consensus of the working group was that it would be
tients in parallel with ongoing moderate symptoms, with useful to base the definition of symptomatic remission on
some individuals developing coping mechanisms that en- the more innovative and heuristic dimensional approach
able them to function despite their illness. The working to descriptive psychopathology.

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REMISSION IN SCHIZOPHRENIA

Dimensions of psychopathology are typically identified phrenia symptoms across three subscales: positive symp-
by using the statistical techniques of factor analysis. Nu- toms (items P1P7, including hallucinatory behavior,
merous factor analytic studies have been conducted, with delusions, and conceptual disorganization), negative
highly replicable results (4147). Three dimensions have symptoms (items N1N7, including blunted affect, social
been identified. The first, a negative symptom dimension and emotional withdrawal, and lack of spontaneity), and
(also referred to as psychomotor poverty), includes pov- general psychopathology symptoms (items G1G16, in-
erty of speech, decreased spontaneous movement, un- cluding mannerisms and posturing, unusual thought con-
changing facial expression, paucity of expressive gesture, tent, and lack of insight). Each item is scored on a scale
affective nonresponse, and lack of vocal inflection. The ranging from 1 (absent) to 7 (extreme), with item ratings
second, a disorganization dimension, includes symptoms incorporating the behavioral effect of symptoms as well as
of inappropriate affect, poverty of content of speech, tan- their severity. The BPRS (55) is an 18-item scale originally
gentiality, derailment, pressure of speech, and distractibil- formulated by using a 7-point range from 1 (not present)
ity. The third, a psychoticism dimension (also called real- to 7 (most severe), although a 6-point version (0, not
ity distortion), includes hallucinations and delusional present, to 6, most severe) also exists. Ratings are based on
ideas. These results confirm the importance of negative clinical observations of symptoms (tension, emotional
symptoms and suggest that positive symptoms should withdrawal, mannerisms and posturing, motor retarda-
be further subdivided into a psychotic and a disorganiza- tion, and uncooperativeness) and subjects verbal report
tion dimension. of symptoms (conceptual disorganization, unusual
However, factor analysis demonstrates only that symp- though content, anxiety, guilt feelings, grandiosity, de-
toms are correlated with one another in the specific groups pressive mood, hostility, somatic concern, hallucinatory
of patients studied. The dimensions identified by factor behavior, suspiciousness, and blunted affect) (56).
analysis can be considered to be valid only if they have Based on an examination of these scales, the working
meaningful relationships with other clinical or biological group identified appropriate criteria to serve as the basis
measures. The validity of these dimensions has been sup- for defining symptomatic remission in schizophrenia. The
ported by studies demonstrating relationships with neuro- goal was to align significant research on symptom factors
psychological measures, longitudinal course, and neuro- in schizophrenia and their practically applied outcome
imaging measures (41, 42, 4852). It has been posited that (DSM-IV criteria) with major symptom domains that sig-
although medication may have differential effects on these nificantly affect the course of illness. Although the work-
three dimensions, they represent related but distinguish- ing group recognized that a variety of symptom domains
able components of the disease process in schizophrenia. (e.g., depression, anxiety) also affect patient outcome and
The DSM-IV diagnostic criteria for schizophrenia closely well-being, consensus was reached to maintain a focused,
align with the three dimensions identified in the factor diagnostic-based definition. In addition, the working
analyses reviewed here, representing the application of group proposed that remission criteria might be described
such concepts to clinical practice. Agreeing on the value of separately for positive and negative symptoms, to allow
this widely accepted application, the working group then primary consideration of these symptom groups indepen-
considered assessment instrument(s) on which an opera- dently in the assessment of symptomatic remission. It
tional definition of symptom remission could be practi- should be noted that a potential complication in the as-
cally based. Subsequently, three validated, widely used sessment of negative symptoms is the possibility that
assessment scales were identified: 1) a single scale repre- symptoms in certain domains, such as anhedonia, may be
sented by the Scale for the Assessment of Positive Symp- secondary (as a side effect of neuroleptic treatment or a
toms (SAPS) and the Scale for the Assessment of Negative symptom of comorbid depression) rather than primary.
Symptoms (SANS) (52, 53), 2) the Positive and Negative Likewise, positive symptoms may sometimes be second-
Syndrome Scale (54), and 3) the Brief Psychiatric Rating ary (e.g., agitated disorganized behavior secondary to
Scale (BPRS) (55). akathisia).
The SAPS, a 34-item scale used to assess positive symp- Specific items selected for consideration as criteria for
toms in schizophrenia, is designed for use in conjunction remission in schizophrenia were chosen to map the three
with the 25-item SANS, which is used to assess negative dimensions of psychopathology identified by factor analy-
symptoms; scoring ranges from 0 (no abnormality) to 5 ses and the five criteria for schizophrenia specified in
(severe). Ratings from the SAPS and SANS (52, 53) are di- DSM-IV (see Table 2 for details). With regard to severity,
vided into three symptom dimensions, including psychot- the working group consensus defined a score of mild or
icism (hallucinations and delusions), negative symptoms less (Positive and Negative Syndrome Scale item scores of
(affective flattening, alogia, avolition-apathy, and anhe- 3; BPRS item scores of 3, using the 17 range for each
donia-asociality), and disorganization (inappropriate af- item; SAPS and SANS item scores of 2) simultaneously on
fect, bizarre behavior, and formal thought disorder) (45). all items as representative of an impairment level consis-
The Positive and Negative Syndrome Scale (54) is a 30- tent with symptomatic remission of illness. Given the
item inventory assessing the absence or severity of schizo- long-term course and intrinsic character of schizophrenia,

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ANDREASEN, CARPENTER, KANE, ET AL.

TABLE 2. Proposed Items for Remission Criteria With Cross-Scale Correspondence and Relationship to Historical Constructs
of Psychopathology Dimensions and DSM-IV Criteria for Schizophreniaa
Proposed Remission Criteria Items
Scale for Assessment of Positive
Symptoms (SAPS) and Scale for
Assessment of Negative Symptoms Positive and Negative Brief Psychiatric Rating Scale
(SANS) Items Syndrome Scale Items (BPRS) Items
Dimension of DSM-IV Global Rating Item Item
Psychopathology Criterion Criterion Item Number Criterion Number Criterionb Number
Psychoticism (reality Delusions Delusions (SAPS) 20 Delusions P1 Grandiosity 8
distortion)
Suspiciousness 11
Unusual thought G9 Unusual thought 15
content content
Hallucinations Hallucinations 7 Hallucinatory P3 Hallucinatory 12
(SAPS) behavior behavior
Disorganization Disorganized Positive formal 34 Conceptual P2 Conceptual 4
speech thought disorganization disorganization
disorder (SAPS)
Grossly Bizarre behavior 25 Mannerisms/ G5 Mannerisms/ 7
disorganized (SAPS) posturing posturing
or catatonic
behavior
Negative symptoms Negative Affective flattening 7 Blunted affect N1 Blunted affect 16
(psychomotor symptoms (SANS)
poverty)
Avolition-apathy 17 Social withdrawal N4 No clearly related
(SANS) symptom
Anhedonia- 22
asociality (SANS)
Alogia (SANS) 13 Lack of spontaneity N6 No clearly related
symptom
a For symptomatic remission, maintenance over a 6-month period of simultaneous ratings of mild or less on all items is required. Rating scale
items are listed by item number.
b Use of BPRS criteria may be complemented by use of the SANS criteria for evaluating overall remission.

the working group consensus defined a period of 6 of these criteria, the working group proposed parallel,
months as a minimum time threshold during which the cross-scale remission criteria items (Table 2). As part of
aforementioned symptom severity must be maintained to the evaluation of the proposed remission criteria, and to
achieve remission. When the BPRS is used in assessment, expand knowledge about the relationship of remission to
the possibility of including the SANS should be consid- recovery of functioning, both academic and commercial
ered, to provide complementary information on negative interests should include metrics of patient functioning in
symptom items in achieving the criteria for overall (posi- future clinical investigations. The implementation of
tive and negative) symptomatic remission. criteria for symptomatic remission will support efforts
In consideration of clinical realities and research inter- around the development of criteria for recovery from
ests, the working group consensus provided that in addi- schizophrenia, which is conceptually related to and facili-
tion to meeting the criteria, individuals may remain in re- tated by symptom stabilization and remission.
mission while experiencing minor changes in symptoms,
in the absence of appreciable effects on daily function or Conclusions
subjective well-being. Ongoing or emerging thoughts re-
garding self-harm or harm of others were considered to be The Remission in Schizophrenia Working Group was
a critical focus for clinical care; the relationship of these formed to develop criteria for symptomatic remission in
thoughts to remission may depend on their presence as patients with schizophrenia, in a manner similar to con-
part of a depressive versus psychotic disorder. sensus development in mood and anxiety disorders. The
Implementation of these criteria should provide re- timeliness of these criteria is reinforced by the growing un-
searchers and clinicians with a robust, well-defined out- derstanding of disease course, by evolving treatment op-
come goal in the long-term treatment of schizophrenia, tions, and by the constrained outcome expectations held
facilitating comparisons of effectiveness across therapeu- by affected individuals, care providers, and clinicians.
tic modalities. Moreover, the use of these criteria may These criteria are proposed with the goals of further exam-
more closely align the interests and goals of clinicians, ining their validity and utility and of providing momen-
professional organizations, commercial entities, and reg- tum and support for definitions of recovery or for other
ulatory agencies with those of patients, their families, and types of definitions that would include functional criteria.
caregivers. To facilitate the adoption and implementation The ability to incorporate the growing amount of informa-

Am J Psychiatry 162:3, March 2005 http://ajp.psychiatryonline.org 447


REMISSION IN SCHIZOPHRENIA

tion related to cognitive dysfunction remains present, 10. Miller JR: Multiple sclerosis, in Merritts Neurology, 10th ed. Ed-
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use of these criteria should help to facilitate comparisons anxiety disorders. J Clin Psychiatry 2003; 64(suppl 15):4045
of effectiveness across the range of available therapeutic 12. van Os J: Is there a continuum of psychotic experiences in the
options and to support a positive, longer-term approach general population? Epidemiol Psichiatr Soc 2003; 12:242252
regarding outcome for patients with schizophrenia. 13. McGorry PD, McFarlane C, Patton GC, Bell R, Hibbert ME, Jack-
son HJ, Bowes G: The prevalence of prodromal features of
schizophrenia in adolescence: a preliminary survey. Acta Psy-
Received May 18, 2004; revision received Aug. 3, 2004; accepted
chiatr Scand 1995; 92:241249
Aug. 30, 2004. From the Department of Psychiatry, University of
Iowa, Iowa City, Iowa; The MIND Institute and the Departments of 14. Hamilton M: A rating scale for depression. J Neurol Neurosurg
Psychiatry, Neurology, and Neuroscience, University of New Mexico, Psychiatry 1960; 23:5662
Albuquerque, N.M.; Maryland Psychiatric Research Center, Balti- 15. Nierenberg AA, Wright EC: Evolution of remission as the new
more; Zucker Hillside Hospital, Glen Oaks, N.Y.; Janssen Pharmaceu- standard in the treatment of depression. J Clin Psychiatry 1999;
tica Products, LP; UCLA Neuropsychiatric Institute, Los Angeles; and 60(suppl 22):711
the National Institute of Mental Health, Bethesda, Md. Address corre- 16. Thase ME: Redefining antidepressant efficacy toward long-
spondence and reprint requests to Dr. Lasser, Janssen Pharmaceutica term recovery. J Clin Psychiatry 1999; 60(suppl 6):1519
Products, LP, 1125 Trenton-Harbourton Rd., Office A20904, Titusville,
17. Ferrier IN: Characterizing the ideal antidepressant therapy to
NJ 08560-0200; rlasser@janus.jnj.com (e-mail).
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Logistical support for a single-day Remission in Schizophrenia
Working Group meeting, including consultative fees, was provided by 18. Ballenger JC, Davidson JR, Lecrubier Y, Nutt DJ, Baldwin DS,
Janssen Pharmaceutica Products, LP, Titusville, N.J. Subsequent ef- den Boer JA, Kasper S, Shear MK: Consensus statement on
forts to refine the criteria and develop the consensus into a manu- panic disorder from the International Consensus Group on De-
script for publication were not financially supported. Dr. Lasser is an pression and Anxiety. J Clin Psychiatry 1998; 59(suppl 8):4754
employee of Janssen Pharmaceutica Products, LP. Review of and sup- 19. Nierenberg AA, DeCecco LM: Definitions of antidepressant
port for the consensus criteria were provided by international ex- treatment response, remission, nonresponse, partial response,
perts in a February 2004 meeting sponsored by Johnson & Johnson; and other relevant outcomes: a focus on treatment-resistant
meeting participants included Thomas Burns, M.D., Roberto Caval-
depression. J Clin Psychiatry 2001; 62(suppl 16):59
laro, M.D., Ph.D., Stefan Leucht, M.D., Bernard Lachaux, M.D., Miquel
Bernardo, M.D., Celso Arango, M.D., Lars Helldin, M.D., Wolfgang 20. Sheehan DV: Defining remission in generalized anxiety disor-
Fleischhacker, M.D., Jim van Os, M.D., Ph.D., and Joseph Peuskens, der: venlafaxine extended release comparative data. J Clin Psy-
M.D., Ph.D. chiatry 2001; 62(suppl 19):2631
21. Kordy H, Kramer B, Palmer RL, Papezova H, Pellet J, Richard M,
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